Table 1.
Characteristics of patients included, setting, oxygenation protocols and outcomes of the three recent trials on oxygen targets in critically ill patients
| TRIAL | BOX trial | EXACT trial | PILOT trial |
|---|---|---|---|
| Type of population | Adult patients comatose after out of hospital cardiac arrest resuscitation | Adult with return of spontaneous circulation after out of hospital cardiac arrest |
Adult undergoing invasive mechanical ventilation in ED with planned admission to ICU, or in ICU (12% cardiac arrest, 30% sepsis-septic shock, 60% with respiratory failure) |
| Sites, country | 2 hospitals, Denmark | 2 emergency medical services, 15 hospitals, Australia | 1 hospital, United States |
| Patients (n) | 789 | 425 | 2541 |
| Time of randomization | Median (IQR) 146 (113–187) min after cardiac arrest | Median (IQR) 64 (51–80) min after cardiac arrest | Median (IQR) 0 (0–5) hours after initiation of mechanical ventilation |
| Target lower group | PaO2 9–10 kPa (68–75 mmHg) | SpO2 90–94% | SpO2 90% (88–92%) |
| Target intermediate group | No | No | SpO2 94% (92–96%) |
| Target higher group | PaO2 13–14 kPa (98–105 mmHg) | SpO2 98–100% | SpO2 98% (96–100%) |
| Achievement lower group | Median PaO2 between 11–12.5 kPa (83–94 mmHg) from 6 to 48 ha | At the end of protocol: median (IQR) SpO2 98 (95–100) %; PaO2 13 (10–19.5) kPa 97 (73–146) mmHg) | Median (IQR) SpO2 94 (92–96) |
| Achievement intermediate group | No | No | Median (95% CI) SpO2 95 (94–97) |
| Achievement higher group | Median PaO2 between 13–14 kPa (98–105 mmHg) from 6–48 ha | At the end of protocol: median (IQR) SpO2 99 (97–100) %; PaO2 15 (11–23,5) kPa 114 (83–177) mmHg) | Median (95% CI) SpO2 97 (96–98) |
| Differences in O2 targets between groups | SpO2 0.5–2.3%b (approx 1.5–2 kPa (11–15 mmHg)a | End of protocol difference in median SpO2 2%, PaO2 2 kPa (15 mmHg) |
SpO2 Median (95% CI): Higher vs Intermediate: 2.0 (1.8–2.2)% Higher vs Lower: 3.2 (3.0–3.5)% Intermediate vs Lower: 1.2 (1.0–1.5) |
| Duration of protocol | From hospital admission to extubation: median time (IQR) 57 (39–110) and 60 (IQR 40–111) hours in lower and higher target groups, respectively | From return of spontaneous circulation to first blood gas analysis in intensive care unit: median ~ 240 (180–320) min | Early after intubation until extubation, transfer to other unit, or end of the 2 month study period: half the patients ~ 72 h |
| Limitations in the oxygenation protocol | Similar PaO2 in the 2 groups in the first 4 h; data available only for the first 48 h; no analysis on PaO2 differences between groups | Limitations in accurate FiO2 titration and compliance to protocol for methods available in EMS. Similar SpO2 in the last hours of treatments (after hospital admission) | PaO2 values available for approx. 20% of patients at day 1 and even less during the other study days, with decreasing differences between groups during the study |
| Primary endpoint | Death or hospital discharge with disability or coma: 32.0% and 33.9% in lower and higher target groups, respectively. (HR 0.95; 95% CI 0.75–1.21; p = 0.69) |
Survival to hospital discharge: 38.3% and 47.9%; unadjusted OR 0.68 [95% CI 0.46–1.00]; (p = 0.05) in lower and higher target groups |
Ventilator-free days through day 28 (median, IQR): 20 (0–25) days in lower target group, 21 (0–25) days in intermediate target group, 21 (0–26) in higher target group (p = 0.81) |
| Mortality | At 90 days: 28.7% and 31.1% in lower and higher target groups, respectively | As above | At 28 days: 34.8%, 34%, 33.2% in the lower, intermediate and higher groups, respectively |